Studies on the cytotoxicity and chemotherapeutic activity of copper and the copper specific ligand, 2,9-dimethyl-1,10-phenanthroline have been extended to representatives of other classes of copper binding ligands. These include diethyldithiocarbamate, ethylenebis]dithiocarbamate] and pyrithione. The copper chelates of these ligands were toxic to L1210 cells in vitro and this toxicity was correlated with their ability to deliver copper to the cells. Treatment of mice bearing the L1210 lymphoma with copper and these ligands was limited by host toxicity, and attempts to reduce host toxicity by administration of a rescue agent, such as dimercaptopropanesulfonic acid was successful but did not improve the chemotherapeutic action. A combined treatment of copper, 2,9-dimethyl-1, 10-phenanthroline and melphalan resulted in cures (70 day survivors) at a dose of melphalan which by itself was not therapeutically effective.